​Research Images

Psoriasis and other skin diseases may be caused by disturbances in the balance between the growth and the differentiation of keratinocytes, the major cell type in the outer layer of skin. We have found that a lipid molecule called sphingosine-1-phosphate (S1P) plays a key role in controlling the differentiation of keratinocytes. Mice missing the gene controlling intracellular S1P concentrations suffered from stunted growth and thickened skin that was prone to peeling within the first few days of life (image to the right). Most of the mutant mice died, but the ones that survived had skin abnormalities—their keratinocytes had high concentrations of S1P, which enhanced keratinocyte differentiation. The findings suggest that manipulating S1P concentrations may be a way to alter the abnormal growth and differentiation of keratinocytes. This suggests that one possible treatment for psoriasis—a disorder in which there is a hyperproliferation of keratinocytes—might be to increase S1P concentrations. (M.L. Allende, L.M. Sipe, G. Tuymetova, K.L. Wilson-Henjum, W. Chen, and R.L. Proia; J Biol Chem 288:18381–18391, 2013)